Palladium-catalyzed tandem annulation: A strategy to construct 2,3-difunctionalized benzofuran derivatives in ionic liquids

Article abstract of DOI:10.1021/acs.joc.5b00154

An efficient and ecofriendly method for the construction of 2,3-difunctionalized benzofuran derivatives in moderate to good yields from readily available 2-alkynylphenols has been developed. This tandem annulation process, featuring one pot, three steps,

Full text of DOI:10.1021/acs.joc.5b00154

Article
pubs.acs.org/joc
Palladium-Catalyzed Tandem Annulation: A Strategy To Construct
2,3-Difunctionalized Benzofuran Derivatives in Ionic Liquids
Jianxiao Li, Zhongzhi Zhu, Shaorong Yang,* Zhenming Zhang, Wanqing Wu, and Huanfeng Jiang*
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China
S
* Supporting Information
ABSTRACT: An efficient and ecofriendly method for the
construction of 2,3-difunctionalized benzofuran derivatives in
moderate to good yields from readily available 2-alkynylphe-
nols has been developed. This tandem annulation process,
featuring one pot, three steps, good functional group tolerance,
and high atom economy, makes this transformation efficient
and practical. Moreover, this protocol is scalable, illustrating
its potential applications in synthetic and pharmaceutical
chemistry.
Scheme 1. Cyclization of 2-Alkynylphenol to
2,3-Difunctionalized Benzofurans
INTRODUCTION
■
The shortage of resources and the increasing awareness of
environmental aspects have changed the major focus of
contemporary chemical research to provide desired target
molecules via an economical and environmentally benign
synthetic route.1 Toward this end, transition-metal-catalyzed
carbon−carbon or carbon−heteroatom bond formation has
attracted considerable attention over the past decades, owing to
its easy access to highly functionalized complicated molecules in
a rather efficient, atom- and step-economical way.2 Particularly,
palladium-catalyzed tandem reaction is now established as a
captivating branch of organic chemistry, since such reactions
afford unconventional and more elaborated poly- and hetero-
cyclic scaffolds via straightforward and efficient synthetic
strategies.3 Besides, the outstanding potential of palladium-
catalyzed tandem processes lies in (i) the diversity of available
bond-forming processes, such as C−C, C−O, and C−N bond
formations; (ii) high chemo-, regio-, and stereoselectivity; and
(iii) great functional-group tolerance. Consequently, palladium-
catalyzed tandem processes constitute an efficient strategy
to synthesize an increasingly wide range of polyfunctionalized
compounds.4
In addition, 2,3-difunctionalized benzofurans are attractive
synthetic targets because of their remarkable biological activities
and potentiality of being pharmaceutical,5 prompting develop-
ment of many efficient synthetic methodologies for constructing
this scaffold. Undoubtedly, 2-alkynylphenols are the most
commonly used precursors to prepare this functionalized core
backbone, for instance, cyclization of 2-alkynylphenol to the
3-metallobenzofuran intermediate that reacts further with an
electrophile to produce the corresponding 2,3-difunctionalized
benzofuran derivatives (Scheme 1, route a).6 After that,
Aurrecoechea and co-workers discovered a new Pd-catalyzed
tandem intramolecular oxypalladation/Heck-type coupling
between 2-alkynylphenols and alkenes leading to 2,3-difunction-
alized benzofuran derivatives (Scheme 1, route b).7 Despite the
significant progress that has been achieved along this line, all
these elegant developments suffer from certain limitations such
as troublesome operation, harsh reaction conditions, or low
yields, prohibiting their wider application in organic synthesis.
Therefore, the development of convenient, efficient, and atom-
economical synthetic methodologies for the rapid construction
of this heterocyclic motif is still highly desirable. In this context,
impressive achievements have been made in enhancing the
efficiency of transition-metal-catalyzed cross-coupling reaction
for the synthesis of 2,3-difunctionalized benzofurans, notably
cross-coupling of C2-halogenated or stannylated benzofurans
with aryl boronic acids or aryl halides,8 direct arylation of
C2- or C3-substituted benzofurans with aryl halides by C−H
activation,9 oxidative dehydrogenative cross-coupling at the C2
position of benzofurans,10 and other strategies.11 More recently,
we reported an intermolecular cascade annulation to construct
functionalized β- and γ-lactones in ionic liquids.12 Driven by our
interest in nucleopalladation13 and Pd-catalyzed cross-coupling
Received: January 20, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00154
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The Journal of Organic Chemistry
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reactions in ionic liquids,14 herein we disclose an efficient and
practical method for the synthesis of 2,3-difunctionalized
benzofurans via the Pd-catalyzed intermolecular tandem annula-
tion reaction of 2-alkynylphenol derivatives with vinylacetic acid in
ionic liquids (Scheme 1, route c).
With the optimized reaction conditions in hand, we further
investigated the scope and generality of this protocol.
Representative results are summarized in Table 2. Gratifyingly,
a range of 2,3-difunctionalized benzofurans 3 were obtained in
moderate to excellent yields. Additionally, reactions employing
2-alkynylphenols 1 with aryl groups attached on the triple bond
all worked well to afford the desired products 3. For instance,
a series of para-substituted aryl rings, including some with
electron-donating groups (R = alkyl, OMe, Ph, ethylcyclohexyl)
and some with electron-withdrawing groups (R = F, Cl, Br), were
converted into the corresponding 2,3-difunctionalized benzofur-
ans in moderate to excellent yields (3aa−3al). Pleasingly, this
transformation was compatible with the Cl- and Br-substituted
aryl rings, which might allow for further synthetic trans-
formations by transition-metal-catalyzed coupling and other
reactions. As for the sterically hindered 2-alkynylphenols 1aa,
1ae, and 1ak, the reaction furnished the corresponding products
3aa in yields similar to those of 3ae and 3ak. These results
showed that this new transformation was tolerant toward
electronic and steric effects of the aromatic ring. Similarly,
2-alkynylphenols 1 with alkyl groups attached on the triple bond
proceeded smoothly to give the products 3 in moderate to good
yields (3am−3bc). Notably, with the carbon chain of alkyl
groups extended, the benzofuran derivatives 3an−3as and 3au−
3ay were successfully obtained in moderate yields. Afterward,
1az−1bc could be transformed efficiently, which greatly
expanded the scope of the products. Besides the wide substrate
scope, another impressive feature of the current tandem annu-
lation reaction is its high tolerance for functional groups. For
instance, the 2-alkynylphenols containing vinyl or thienyl groups
underwent the tandem reaction to give corresponding products
3bd and 3be in 78% and 56% yields, respectively. Unfortunately,
2-(pyridin-2-ylethynyl)phenol (1bf) failed to afford the desired
products. Delightfully, 2,2-dimethylbut-3-enoic acid (2b) could
be converted into the corresponding products 3bg in 87% yield
as well.
With the positive results above, we next explored the scope of
tandem annulation of various substituted phenols with allylic acid
(2a), which showed high tolerance to the reactions. In general,
various substituted 2-alkynylphenols with electron-donating
groups (alkyl, alkoxyl) and weakly or moderately electron-
withdrawing groups (F, Cl, Br) afforded the corresponding
benzofuran derivatives 4a−4n in moderate to excellent yields
(Table 3). Importantly, even if a sterically bulky 2-alkynylphenol
such as 4-(tert-butyl)-2-(phenylethynyl)phenol was used, the
corresponding 4e was obtained in 81% yield. Moreover, this
transformation could be successfully extended to a variety of
2,4- and 2,5-disubstituted 2-alkynylphenols, furnishing the
corresponding benzofuran derivatives 4f and 4n in 76% and
74% yields, respectively.
Based on the results obtained, the tandem annulation reactions
of pent-4-enoic acid (5) with 2-alkynylphenols were attempted
under standard reaction conditions (Scheme 2). When the
tandem annulation coupling reagent was 2-(phenylethynyl)-
phenol (1aa), no benzofuran products 8 were obtained, but 6a
and 7a were obtained in 84% and 11% yields, respectively.
Similarly, when 2-(pent-1-yn-1-yl)phenol (1ao) was used as the
coupling reagent, the annulation products 6b (66%) and 7b
(19%) were obtained, respectively. The result obtained indicates
the crucial role of the position of the carboxylic acid pattern in the
transformation.
RESULTS AND DISCUSSION
■
Our investigation was initiated by using the reaction of
2-(phenylethynyl)phenol (1aa) with but-3-enoic acid (2a) as a
model system to screen the optimal conditions (Table 1). First,
a
Table 1. Optimization of the Reaction Conditions
b
yield
entry
catalyst
PdCl2
oxidant
solvent
(%)
1
CuCl2·2H2O
Cu(OAc)2
Cu(OTf)2
Cu(OPiv)2
[C2OHmim]Cl
[C2OHmim]Cl
[C2OHmim]Cl
[C2OHmim]Cl
23
2
PdCl2
17
3
PdCl2
trace
trace
67
4
PdCl2
5
PdCl2
Cu(TFA)2·xH2O [C2OHmim]Cl
Cu(hfac)2·2H2O [C2OHmim]Cl
Cu(TFA)2·xH2O [C2OHmim]Cl
6
PdCl2
10
7
Pd(TFA)2
Pd(TFA)2
Pd(OAc)2
Pd(PhCN)2Cl2
Pd(acac)2
Pd(PCy3)2Cl2
[Pd(η3-C3H5)Cl]2 Cu(TFA)2·xH2O [C2OHmim]Cl
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
94 (83)
58
8
O2
[C2OHmim]Cl
9
Cu(TFA)2·xH2O [C2OHmim]Cl
Cu(TFA)2·xH2O [C2OHmim]Cl
Cu(TFA)2·xH2O [C2OHmim]Cl
Cu(TFA)2·xH2O [C2OHmim]Cl
trace
19
10
11
12
13
14
15
16
8
52
43
Cu(TFA)2·xH2O DMF
Cu(TFA)2·xH2O toluene
Cu(TFA)2·xH2O 1,4-dioxane
trace
9
trace
a
Unless otherwise noted, all reactions were performed with 1aa
(0.25 mmol), 2a (0.3 mmol), Pd catalyst (3 mol %), and oxidant (2 equiv)
b
in the indicated solvent (1.0 mL) at 100 °C for 12 h. Determined by GC
using dodecane as the internal standard. The value in parentheses is
the yield of isolated product. Hfac = hexafluoroacetylacetonate.
with the combination of PdCl2 and CuCl2·2H2O in [C2OHmim]
Cl at 100 °C, the desired product 3aa was obtained in 23% yield
1
(Table 1, entry 1). The structure of 3aa was established by H
NMR, 13C NMR, GC−MS, and HRMS analysis. Subsequently,
further exploration of oxidants in the model reaction indicated
that Cu(TFA)2·xH2O was superior to the others. Other oxidants,
such as Cu(OAc)2, Cu(OTf)2, Cu(OPiv)2, and Cu(hfac)2·2H2O,
showed less or no efficiency in terms of chemical yields (Table 1,
entries 2−6). Unfortunately, a lower yield of 3aa was obtained
when the reaction was performed under 1 atm of pressure of O2
(Table 1, entry 8). Furthermore, other palladium catalysts
were also examined. Except for Pd(TFA)2, other Pd sources,
including Pd(OAc)2, Pd(PCy3)2Cl2, Pd(PhCN)2Cl2, Pd(acac)2,
and [Pd(η3-C3H5)Cl]2, showed low efficiencies (entries 9−13).
Replacing [C2OHmim]Cl with other ionic liquids, such as
[Bmim]Cl, [Bmim]BF4, [Bmim]PF6, [C2O2mim]Cl, and
[BuPy]Cl, were ineffective for this transformation, and the
reactions gave only low yields.15 Finally, various conventional
solvents, such as DMF, toluene, and 1,4-dioxane, were examined
under the same reaction conditions and significantly decreased
the yields (entries 14−16).
To prove the practicality of the present method in the
synthesis of benzofuran derivatives, a gram-scale synthesis of 3aa
B
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a
Table 2. Scope of the Reaction of 2-Alkyl-Substituted Phenols with But-3-enoic Acid
a
Reaction conditions: 1 (0.25 mmol), 2 (0.30 mmol), Pd(TFA)2 (3 mol %), Cu(TFA)2·xH2O (2 equiv), and [C2OHmim]Cl (1 mL) at 100 °C.
Reaction was monitored by TLC for the completion of the reaction. Yields referred to isolated yields.
was performed, and the result is shown in Scheme 3. When 0.97 g
of 1aa was utilized, 1.02 g of product 3aa was obtained in 74%
yield.
Based on the current results and previous literature,12−14,18
the postulated reaction mechanism is depicted in Scheme 6.
Pd complex is initially formed in situ in ionic liquids.12−14 Then,
oxypalladation of 2-alkynylphenols afforded vinyl palladium
intermediate I.18 Subsequently, intermediate I could undergo
Heck-like alkene insertion to produce intermediates II.
Simultaneously, the alkylpalladium species coordinated to the
oxygen atoms of the hydroxyl group and generated the five
membered palladacycle intermediate III.12 Finally, a reductive
elimination produced the target product and Pd(II) active species
was regenerated by the oxidation of Cu(II) for the next cycle.
To extend the applicability of this methodology, we
subsequently utilized various 2-(phenylethynyl)anilines 9 with
the developed optimal reaction conditions. Disappointingly,
2-(phenylethynyl)aniline (9a) and N-methyl-2-(phenylethynyl)-
aniline (9b) failed to afford the desired products and only a
complicated mixture was detected by GC−MS. Ultimately, when
4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide
(9c) was employed to react with 2a under the standard con-
ditions, only a trace amount of 1-tosyl-1H-indole 10c was
detected by GC−MS (Scheme 4).
The aryl halide functionality in the newly formed product
enables them to be attractive and versatile synthetic building
blocks in a variety of chemical transformations, leading to more
complicated organic architectures by the formation of new C−C
bonds. Hence, to demonstrate the synthetic utility of this
protocol, we further examined the resultant products in the
transition-metal-catalyzed cross-coupling reactions (Scheme 5).
For instance, the Suzuki−Miyaura cross-coupling reactions of 4l
with phenylboronic acid delivered arylated compounds 11a in
moderate yield.16 Furthermore, the desulfitative coupling of 4l
occurred uneventfully as well, providing the arylated compounds
11b in 68% yield.17 To our satisfaction, 4l underwent the Negishi
coupling to produce the highly functionalized benzofuran
derivative 11c in 63% yield.16
CONCLUSION
■
In conclusion, we have successfully accomplished an attractive
strategy for the synthesis of functionalized 2,3-difunctionalized
benzofurans via palladium-catalyzed cascade annulation of
2-alkynylphenols with allylic acids in ionic liquids. This cascade
annulation process, featuring one pot, three steps, good
functional group tolerance, and high atom economy, makes
this transformation efficient and practical. Most importantly, the
employment of ionic liquids under mild conditions makes this
transformation green and environmentally friendly. Further-
more, this protocol should provide an ecofriendly methodology
to functionalized benzofurans.
EXPERIMENTAL SECTION
■
General Methods. Melting points were measured by a melting
point instrument and were uncorrected. 1H and 13C NMR spectra were
C
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a
Table 3. Scope with Regard to But-3-enoic Acid and Substituted Phenols
a
Reaction conditions: 1 (0.25 mmol), 2a (0.30 mmol), Pd(TFA)2 (3 mol %), Cu(TFA)2·xH2O (2 equiv), and [C2OHmim]Cl (1 mL) at 100 °C.
Reaction was monitored by TLC for the completion of the reaction. Yields referred to isolated yields.
Scheme 2. Investigation of Tandem Annulation of Pent-4-enoic Acid with Substituted Phenols
a
Scheme 3. Gram-Scale Synthesis of 3aa
Scheme 4. Investigation of Tandem Annulation of 2a with
2-Alkyl-Substituted Anilines
a
Reaction conditions: 1aa (5 mmol, 0.97 g), but-3-enoic acid 2a
(6 mmol, 0.52 g), Pd(TFA)2 (3 mol %, 50 mg), Cu(TFA)2·xH2O
(2 equiv, 2.89 g), and [C2OHmim]Cl (3 mL) at 100 °C for 28 h.
Reaction was monitored by TLC for the completion of the reaction;
Yields referred to isolated yields.
D
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1776, 1645, 1515, 1453, 1136, 750; MS (EI) m/z 105, 115, 128, 139,
165, 191, 219, 249, 278; HRMS(ESI) m/z calcd for C18H15O3 [M + H]+
279.1016, found 279.1013.
Scheme 5. Synthetic Transformations of 4l
4-((2-(4-Propylphenyl)benzofuran-3-yl)methyl)oxetan-2-one
(3ab): yield 89% (71.2 mg) as a yellow oil; Rf 0.35 (petroleum ether/
EtOAc 5/1); 1H NMR (400 MHz, CDCl3) δ 7.58 (t, J = 6.8 Hz, 3H),
7.53 (d, J = 8.4 Hz, 1H), 7.33 (t, J = 7.6 Hz, 3H), 7.27 (d, J = 8.0 Hz, 1H),
5.91 (t, J = 8.0 Hz, 1H), 2.86−2.76 (m, 2H), 2.74−2.59 (m, 4H), 1.79−
1.64 (m, 2H), 0.98 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
176.6, 154.4, 154.1, 144.5, 129.1, 128.0, 127.1, 126.8, 124.8, 123.1, 120.4,
112.9, 111.6, 76.0, 37.9, 29.6, 28.6, 24.4, 13.8 ppm; νmax(KBr)/cm−1
3058, 2926, 1766, 1640, 1515, 1416, 1124; MS (EI) m/z 91, 115, 147,
189, 207, 233, 265, 291, 320; HRMS(ESI) m/z calcd for C21H21O3
[M + H]+ 321.1485, found 321.1483.
4-((2-(4-Butylphenyl)benzofuran-3-yl)methyl)oxetan-2-one (3ac):
yield 88% (73.5 mg) as a yellow oil; Rf 0.35 (petroleum ether/EtOAc
5/1); 1H NMR (400 MHz, CDCl3) δ 7.58 (t, J = 7.2 Hz, 3H), 7.53 (d, J =
8.4 Hz, 1H), 7.33 (t, J = 7.2 Hz, 3H), 7.27 (d, J = 7.6 Hz, 1H), 5.91 (t, J =
8.0 Hz, 1H), 2.81 (dd, J = 16.8, 7.6 Hz, 2H), 2.76−2.60 (m, 4H), 1.65
(dt, J = 15.2, 7.6 Hz, 2H), 1.39 (dq, J = 14.6, 7.2 Hz, 2H), 0.95 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 176.7, 154.4, 154.1, 144.7,
129.0, 128.0, 127.1, 126.8, 124.8, 123.1, 120.4, 112.9, 111.6, 76.0, 35.5,
33.4, 29.6, 28.6, 22.3, 13.9 ppm; νmax(KBr)/cm−1 3055, 2929, 1754,
1637, 1516, 1426, 1128; MS (EI) m/z 115, 131, 145, 187, 199, 217, 229,
272, 281, 334; HRMS(ESI) m/z calcd for C22H23O3 [M + H]+
335.1642, found 335.1637.
Scheme 6. Proposed Mechanism
4-((2-(4-Pentylphenyl)benzofuran-3-yl)methyl)oxetan-2-one
(3ad): yield 83% (72.2 mg) as a yellow oil; Rf 0.37 (petroleum ether/
EtOAc 5/1); 1H NMR (400 MHz, CDCl3) δ 7.58 (t, J = 7.2 Hz, 3H),
7.53 (d, J = 8.0 Hz, 1H), 7.33 (t, J = 7.2 Hz, 3H), 7.27 (d, J = 7.6 Hz, 1H),
5.91 (t, J = 8.0 Hz, 1H), 2.81 (dd, J = 16.8, 7.6 Hz, 2H), 2.75−2.58 (m,
4H), 1.73−1.62 (m, 2H), 1.42−1.30 (m, 4H), 0.91 (t, J = 6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 176.7, 154.4, 154.1, 144.8, 129.0, 128.0,
127.1, 126.8, 124.8, 123.1, 120.4, 112.9, 111.6, 76.0, 35.8, 31.5, 30.9,
29.6, 28.6, 22.5, 14.0 ppm; νmax(KBr)/cm−1 3053, 2928, 1755, 1631,
1518, 1426, 1126; MS (EI) m/z 115, 133, 165, 191, 207, 233, 281, 320,
348; HRMS(ESI) m/z calcd for C23H25O3 [M + H]+ 349.1798, found
349.1795.
4-((2-(4-Hexylphenyl)benzofuran-3-yl)methyl)oxetan-2-one
(3ae): yield 85% (76.9 mg) as a yellow oil; Rf 0.40 (petroleum ether/
EtOAc 5/1); 1H NMR (400 MHz, CDCl3) δ 7.58 (t, J = 7.2 Hz, 3H),
7.53 (d, J = 8.0 Hz, 1H), 7.33 (t, J = 7.6 Hz, 3H), 7.27 (d, J = 7.6 Hz, 1H),
5.91 (t, J = 8.0 Hz, 1H), 2.81 (dd, J = 16.8, 7.6 Hz, 2H), 2.74−2.60
(m, 4H), 1.69−1.62 (m, 2H), 1.40−1.30 (m, 6H), 0.89 (t, J = 6.8 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 176.7, 154.4, 154.1, 144.8, 129.0,
128.0, 127.1, 126.8, 124.8, 123.1, 120.4, 112.9, 111.6, 76.0, 35.8, 31.7,
31.3, 29.6, 28.9, 28.6, 22.6, 14.1 ppm; νmax(KBr)/cm−1 3050, 2930,
1748, 1622, 1518, 1424, 1123; MS (EI) m/z 115, 165, 207, 233, 291,
307, 362; HRMS(ESI) m/z calcd for C24H27O3 [M + H]+ 363.1955,
found 363.1952.
4-((2-(4-(tert-Butyl)phenyl)benzofuran-3-yl)methyl)oxetan-2-one
(3af): yield 83% (69.3 mg) as a yellow oil; Rf 0.38 (petroleum ether/
EtOAc 5/1); 1H NMR (400 MHz, CDCl3) δ 7.59 (t, J = 6.4 Hz, 3H),
7.53 (d, J = 8.4 Hz, 3H), 7.33 (d, J = 7.6 Hz, 1H), 7.27 (d, J = 8.4 Hz,
1H), 5.92 (t, J = 8.0 Hz, 1H), 2.86−2.73 (m, 2H), 2.72−2.57 (m, 2H),
1.37 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 176.7, 154.4, 154.0, 152.9,
127.9, 126.9, 126.8, 125.9, 124.8, 123.1, 120.5, 112.9, 111.6, 76.0, 34.9,
31.2, 29.6, 28.6 ppm; νmax(KBr)/cm−1 3057, 2959, 1778, 1619, 1509,
1455, 1400, 1135, 747; MS (EI) m/z 105, 119, 133, 154, 193, 207, 249,
281, 334; HRMS(ESI) m/z calcd for C22H22NaO3 [M + Na]+ 357.1461,
found 357.1458.
recorded by using a 400 MHz NMR spectrometer. The chemical shifts
are referenced to signals at 7.24 and 77.0 ppm, respectively, and
chloroform is used as a solvent with TMS as the internal standard. IR
spectra were obtained either as potassium bromide pellets or as liquid
films between two potassium bromide pellets with an infrared
spectrometer. GC−MS was obtained using electron ionization. The
data of HRMS was carried out on a high-resolution mass spectrometer
(LCMS-IT-TOF). TLC was performed by using commercially available
100−400 mesh silica gel plates (GF254). Unless otherwise noted,
all purchased chemicals were used without further purification. The
2-alkynylphenols were prepared according to the literature.7
General Procedure for the Synthesis of 2,3-Disubstituted
Benzofurans 3 and 4. A mixture of 2-alkynylphenols 1 (0.25 mmol),
olefin acids 2 (0.30 mmol), Pd(TFA)2 (2.5 mg, 3 mol %), Cu(TFA)2·
xH2O (145 mg, 2 equiv), and ionic liquid (1.0 mL) was placed in a test
tube (10 mL) equipped with a magnetic stirring bar. The mixture was
stirred under the atmosphere of air at 100 °C. After the reaction was
completed, 10 mL of ethyl acetate (3 × 10 mL) was added into the tube.
The combined organic layers were washed with brine to neutral, dried
over MgSO4, and concentrated in vacuum. Purification of the residue on
a preparative TLC afforded the desired products.
4-((2-(4-Ethoxyphenyl)benzofuran-3-yl)methyl)oxetan-2-one
(3ag): yield 74% (59.6 mg) as a yellow solid; mp = 123.4−124.5 °C; Rf
4-((2-Phenylbenzofuran-3-yl)methyl)oxetan-2-one (3aa): yield
83% (57.7 mg) as a yellow solid; mp = 136.6−137.4 °C; Rf 0.34
(petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3) δ 7.67 (d,
J = 7.6 Hz, 2H), 7.60 (d, J = 7.6 Hz, 1H), 7.51 (dt, J = 13.2, 7.6 Hz, 4H),
7.35 (t, J = 8.0 Hz, 1H), 7.28 (d, J = 7.6 Hz, 1H), 5.92 (t, J = 8.0 Hz, 1H),
2.88−2.78 (m, 2H), 2.73−2.59 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 176.6, 154.5, 153.7, 129.8, 129.5, 128.9, 128.1, 126.7, 124.9, 123.2,
120.6, 113.5, 111.7, 75.9, 29.5, 28.6 ppm; νmax(KBr)/cm−1 3060, 2922,
1
0.41 (petroleum ether/EtOAc 2/1); H NMR (400 MHz, CDCl3) δ
7.60−7.56 (m, 3H), 7.52 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H),
7.27 (d, J = 6.4 Hz, 1H), 7.02 (d, J = 8.4 Hz, 2H), 5.88 (t, J = 8.0 Hz, 1H),
4.11 (q, J = 6.8 Hz, 2H), 2.88−2.78 (m, 2H), 2.74−2.60 (m, 2H), 1.46
(t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 176.7, 160.0, 154.3,
154.1, 129.6, 126.9, 124.6, 123.1, 122.0, 120.3, 114.9, 112.1, 111.5, 76.1,
63.7, 29.6, 28.5, 14.8 ppm; νmax(KBr)/cm−1 3060, 2923, 1775, 1645,
E
DOI: 10.1021/acs.joc.5b00154
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1546, 1510, 1178, 751; MS (EI) m/z 105, 127, 143, 165, 193, 207, 249,
281, 322; HRMS(EI) m/z calcd for C20H19O4 [M + H]+ 323.1278,
found 323.1283.
27.4 ppm; νmax(KBr)/cm−1 3066, 2967, 1777, 1648, 1517, 1455, 1136,
750; MS (EI) m/z 91, 115, 128, 157, 183, 199, 225, 243, 258;
HRMS(EI) m/z calcd for C16H19O3 [M + H]+ 259.1329, found
259.1332.
4-((2-Propylbenzofuran-3-yl)methyl)oxetan-2-one (3an): yield
69% (42.1 mg) as a yellow oil; Rf 0.44 (petroleum ether/EtOAc 5/1);
1H NMR (400 MHz, CDCl3) δ 7.47−7.42 (m, 2H), 7.24−7.18 (m, 2H),
5.68 (t, J = 8.0 Hz, 1H), 2.82−2.72 (m, 4H), 2.56 (dd, J = 16.8, 8.0 Hz,
2H), 1.77 (dq, J = 14.4, 7.2 Hz, 2H), 0.98 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 176.6, 156.4, 154.2, 126.3, 123.9, 122.8, 119.5,
112.7, 111.2, 75.7, 29.4, 28.9, 28.7, 21.7, 13.7 ppm; νmax(KBr)/cm−1
3055, 2938, 1768, 1649, 1509, 1457, 1400, 1135, 748; MS (EI) m/z 91,
103, 115, 131, 145, 189, 215, 244; HRMS(ESI) m/z calcd for C15H17O3
[M + H]+ 245.1172, found 245.1170.
4-((2-(4-Fluorophenyl)benzofuran-3-yl)methyl)oxetan-2-one
(3ah): yield 80% (59.2 mg) as a yellow solid; mp = 110.6−111.9 °C; Rf
1
0.42 (petroleum ether/EtOAc 4/1); H NMR (400 MHz, CDCl3) δ
7.67−7.64 (m, 2H), 7.59 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H),
7.35 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 7.6 Hz, 1H), 7.21 (t, J = 8.0 Hz, 2H),
5.85 (t, J = 8.0 Hz, 1H), 2.88−2.79 (m, 2H), 2.75−2.58 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ 176.5, 163.4 (J = 249.2 Hz), 154.4, 152.9,
130.1 (J = 8.4 Hz), 126.6, 125.9 (J = 3.2 Hz), 125.1, 123.3, 120.5, 116.2
(J = 21.7 Hz), 113.3, 111.7, 75.7, 29.5, 28.5 ppm; νmax(KBr)/cm−1 3063,
2922, 1775, 1644, 1508, 1453, 1416, 1182, 749; MS (EI) m/z 106, 133,
183, 207, 251, 296; HRMS(EI) m/z calcd for C18H14FO3 [M + H]+
297.0921, found 297.0922.
4-((2-Butylbenzofuran-3-yl)methyl)oxetan-2-one (3ao): yield 64%
4-((2-(4-Chlorophenyl)benzofuran-3-yl)methyl)oxetan-2-one
1
(41.3 mg) as a yellow oil; Rf 0.45 (petroleum ether/EtOAc 5/1); H
(3ai): yield 72% (56.2 mg) as a yellow solid; mp = 102.6−103.7 °C; Rf
NMR (400 MHz, CDCl3) δ 7.44 (t, J = 8.4 Hz, 2H), 7.24−7.18 (m, 2H),
5.68 (t, J = 8.0 Hz, 1H), 2.87−2.68 (m, 4H), 2.56 (dd, J = 16.4, 8.0 Hz,
2H), 1.72 (dt, J = 14.8, 7.2 Hz, 2H), 1.38 (td, J = 14.8, 7.2 Hz, 2H), 0.94
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 175.5, 155.5, 153.1,
125.2, 122.8, 121.6, 118.3, 111.3, 110.1, 74.5, 29.4, 28.3, 27.8, 25.4, 21.2,
12.6 ppm; νmax(KBr)/cm−1 3056, 2936, 1763, 1645, 1506, 1450, 1400,
1133, 746; MS (EI) m/z 55, 103, 128, 145, 171, 185, 215, 258;
HRMS(ESI) m/z calcd for C16H19O3 [M + H]+ 259.1329, found
259.1323.
1
0.40 (petroleum ether/EtOAc 4/1); H NMR (400 MHz, CDCl3) δ
7.62−7.60 (m, 3H), 7.54 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H),
7.41−7.34 (m, 1H), 7.29 (d, J = 7.6 Hz, 1H), 5.87 (t, J = 8.0 Hz, 1H),
2.90−2.78 (m, 2H), 2.74−2.58 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 176.5, 154.5, 152.5, 135.7, 130.9, 129.3, 129.2, 128.6, 125.3, 123.4,
120.6, 113.9, 111.7, 75.6, 29.4, 28.6 ppm; νmax(KBr)/cm−1 3064, 2923,
1777, 1648, 1483, 1452, 1137, 750; MS (EI) m/z 115, 135, 165, 193,
207, 233, 255, 281, 312; HRMS(EI) m/z calcd for C18H13ClNaO3
[M + Na]+ 335.0445, found 335.0444.
4-((2-Pentylbenzofuran-3-yl)methyl)oxetan-2-one (3ap): yield
73% (49.6 mg) as a yellow oil; Rf 0.45 (petroleum ether/EtOAc 5/1);
1H NMR (400 MHz, CDCl3) δ 7.44 (t, J = 8.4 Hz, 2H), 7.24−7.18 (m,
2H), 5.68 (t, J = 8.0 Hz, 1H), 2.83−2.75 (m, 4H), 2.56 (q, J = 8.2 Hz,
2H), 1.77−1.70 (m, 2H), 1.39−1.30 (m, 2H), 0.90 (t, J = 6.4 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 176.7, 156.6, 154.2, 126.3, 123.9, 122.7,
119.5, 112.4, 111.2, 75.7, 31.3, 29.4, 28.9, 28.1, 26.8, 22.4, 13.9 ppm;
νmax(KBr)/cm−1 3058, 2938, 1768, 1644, 1506, 1440, 1406, 1130, 748;
MS (EI) m/z 91, 128, 145, 187, 217, 243, 272; HRMS(ESI) m/z calcd
for C17H21O3 [M + H]+ 273.1485, found 273.1483.
4-((2-(4-Bromophenyl)benzofuran-3-yl)methyl)oxetan-2-one
(3aj): yield 77% (68.5 mg) as a yellow solid; mp = 133.7−134.9 °C; Rf
1
0.47 (petroleum ether/EtOAc 4/1); H NMR (400 MHz, CDCl3) δ
7.65 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 7.6 Hz, 1H), 7.54 (d, J = 8.4 Hz,
2H), 7.41−7.34 (m, 2H), 7.29 (d, J = 7.6 Hz, 1H), 5.86 (t, J = 8.0 Hz,
1H), 2.91−2.78 (m, 2H), 2.73−2.60 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 176.4, 154.5, 152.5, 138.1, 132.2, 129.5, 128.7, 126.6, 125.3,
123.4, 120.6, 114.0, 111.7, 75.6, 29.4, 28.5 ppm; νmax(KBr)/cm−1 3066,
2921, 1767, 1645, 1485, 1450, 1131, 756; MS (EI) m/z 115, 133, 165,
207, 233, 267, 301, 327, 356; HRMS(EI) m/z calcd for C18H13BrNaO3
[M + Na]+ 378.9940, found 378.9938.
4-((2-Hexylbenzofuran-3-yl)methyl)oxetan-2-one (3aq): yield 66%
1
4-((2-(4-(4-Ethylcyclohexyl)phenyl)benzofuran-3-yl)methyl)-
(47.2 mg) as a yellow oil; Rf 0.45 (petroleum ether/EtOAc 5/1); H
oxetan-2-one (3ak): yield 78% (75.7 mg) as a yellow solid; mp =
NMR (400 MHz, CDCl3) δ 7.44 (t, J = 8.8 Hz, 2H), 7.24−7.18 (m, 2H),
5.67 (t, J = 8.0 Hz, 1H), 2.84−2.70 (m, 4H), 2.55 (q, J = 8.0 Hz, 2H),
1.72 (dd, J = 14.4, 6.8 Hz, 2H), 1.41−1.32 (m, 6H), 0.87 (d, J = 6.4 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 176.6, 156.6, 154.2, 126.3, 123.9,
122.7, 119.5, 112.4, 111.2, 75.7, 31.5, 29.7, 29.4, 28.9, 28.4, 26.8, 22.5,
14.0 ppm; νmax(KBr)/cm−1 3056, 2936, 1766, 1648, 1502, 1445, 1404,
1128, 754; MS (EI) m/z 55, 85, 115, 131, 145, 171, 201, 215, 232, 286;
HRMS(ESI) m/z calcd for C18H23O3 [M + H]+ 287.1642, found
287.1640.
4-((2-Heptylbenzofuran-3-yl)methyl)oxetan-2-one (3ar): yield
63% (47.3 mg) as a yellow oil; Rf 0.46 (petroleum ether/EtOAc 5/1);
1H NMR (400 MHz, CDCl3) δ 7.44 (t, J = 8.8 Hz, 2H), 7.24−7.18 (m,
2H), 5.67 (t, J = 8.0 Hz, 1H), 2.82−2.74 (m, 2H), 2.55 (dd, J = 16.4, 8.0
Hz, 2H), 1.72 (dd, J = 13.2, 6.4 Hz, 2H), 1.33−1.25 (m, 8H), 0.88 (t, J =
6.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 176.6, 156.6, 154.2, 126.3,
123.9, 122.7, 119.5, 112.4, 111.2, 75.7, 31.7, 29.4, 29.2, 28.9, 28.8, 28.4,
26.8, 22.6, 14.0 ppm; νmax(KBr)/cm−1 3058, 2938, 1763, 1640, 1508,
1448, 1400, 1129, 756; MS (EI) m/z 55, 85, 118, 131, 171, 207, 215, 245,
281, 300; HRMS(ESI) m/z calcd for C19H25O3 [M + H]+ 301.1798,
found 301.1794.
1
130.3−131.3 °C; Rf 0.32 (petroleum ether/EtOAc 5/1); H NMR
(400 MHz, CDCl3) δ 7.58 (d, J = 8.0 Hz, 3H), 7.52 (d, J = 8.0 Hz, 1H),
7.35 (t, J = 8.0 Hz, 2H), 7.31 (d, J = 8.4 Hz, 1H), 7.26 (d, J = 6.8 Hz, 1H),
5.91 (t, J = 8.0 Hz, 1H), 2.88−2.78 (m, 2H), 2.75−2.61 (m, 2H), 2.57−
2.51 (m, 1H), 1.93 (t, J = 11.2 Hz, 4H), 1.53−1.43 (m, 1H), 1.31−1.26
(m, 4H), 1.13−1.03 (m, 2H), 0.92 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 176.7, 154.4, 154.1, 149.6, 128.1, 127.5, 127.2,
126.8, 124.7, 123.1, 120.4, 112.9, 111.6, 76.0, 44.6, 39.1, 34.2, 33.1, 30.0,
29.6, 28.6 ppm; νmax(KBr)/cm−1 3059, 2921, 1778, 1626, 1514, 1453,
1137, 750; MS (EI) m/z 105, 135, 191, 207, 281, 325, 356, 388;
HRMS(EI) m/z calcd for C26H28NaO3 [M + Na]+ 411.1931, found
411.1926.
4-((2-([1,1′-Biphenyl]-4-yl)benzofuran-3-yl)methyl)oxetan-2-one
(3al): yield 82% (72.6 mg) as a yellow solid; mp = 194.3−195.7 °C; Rf
1
0.31 (petroleum ether/EtOAc 4/1); H NMR (400 MHz, CDCl3) δ
7.75 (s, 3H), 7.65 (d, J = 7.2 Hz, 2H), 7.62 (d, J = 8.0 Hz, 1H), 7.56 (d,
J = 8.0 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.42−7.37 (m, 2H), 7.35 (d, J =
8.0 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H), 5.98 (t, J = 8.0 Hz, 1H), 2.90−2.80
(m, 2H), 2.78−2.65 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 176.6,
154.5, 153.5, 142.3, 140.1, 130.1, 129.0, 128.6, 128.5, 127.6, 127.1, 126.8,
125.0, 123.3, 120.6, 113.6, 111.7, 76.0, 29.5, 28.6 ppm; νmax(KBr)/cm−1
3056, 2920, 1775, 1648, 1517, 1500, 1449, 1138, 750; MS (EI) m/z 105,
119, 133, 149, 177, 191, 207, 281, 325, 354; HRMS(EI) m/z calcd for
C24H18NaO3 [M + Na]+ 377.1148, found 377.1145.
4-((2-Octylbenzofuran-3-yl)methyl)oxetan-2-one (3as): yield 57%
1
(44.7 mg) as a yellow oil; Rf 0.46 (petroleum ether/EtOAc 5/1); H
NMR (400 MHz, CDCl3) δ 7.44 (t, J = 8.6 Hz, 2H), 7.24−7.18 (m, 2H),
5.67 (t, J = 8.0 Hz, 1H), 2.84−2.71 (m, 4H), 2.56 (q, J = 8.0 Hz, 2H),
1.72 (dd, J = 14.0, 7.0 Hz, 2H), 1.33−1.25 (m, 10H), 0.87 (t, J = 6.0 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 176.7, 156.7, 154.2, 126.3, 123.9,
122.7, 119.5, 112.4, 111.2, 75.7, 31.8, 29.4, 29.3, 29.2, 29.1, 28.9, 28.4,
26.8, 22.6, 14.1 ppm; νmax(KBr)/cm−1 3060, 2940, 1766, 1643, 1500,
1445, 1405, 1134, 758; MS (EI) m/z 55, 77, 91, 115, 145, 187, 215, 229,
259, 281, 314; HRMS(ESI) m/z calcd for C20H27O3 [M + H]+
315.1955, found 315.1953.
4-((2-(tert-Butyl)benzofuran-3-yl)methyl)oxetan-2-one (3am):
yield 81% (52.2 mg) as a yellow solid; mp = 101.4−102.8 °C; Rf 0.44
1
(petroleum ether/EtOAc 5/1); H NMR (400 MHz, CDCl3) δ 7.45
(d, J = 7.6 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H),
7.17 (t, J = 7.6 Hz, 1H), 6.07 (t, J = 8.0 Hz, 1H), 2.83−2.71 (m, 2H),
2.58−2.51 (m, 2H), 1.47 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 176.7,
161.8, 153.3, 127.0, 122.6, 120.4, 111.2, 111.1, 75.9, 30.0, 29.6, 29.2,
F
DOI: 10.1021/acs.joc.5b00154
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
4-((2-(4-Chlorobutyl)benzofuran-3-yl)methyl)oxetan-2-one (3at):
yield 77% (56.2 mg) as a yellow oil; Rf 0.41 (petroleum ether/EtOAc
5/1); 1H NMR (400 MHz, CDCl3) δ 7.45 (t, J = 8.0 Hz, 2H), 7.24−7.19
(m, 2H), 5.68 (t, J = 8.0 Hz, 1H), 3.57 (t, J = 6.0 Hz, 2H), 2.90−2.81
(m, 2H), 2.80−2.72 (m, 2H), 2.64−2.51 (m, 2H), 1.96−1.80 (m, 4H);
13C NMR (100 MHz, CDCl3) δ 176.6, 155.5, 154.2, 126.2, 124.2, 122.9,
119.5, 112.9, 111.3, 75.5, 44.5, 31.8, 29.3, 28.9, 26.1, 25.7 ppm;
νmax(KBr)/cm−1 3050, 2926, 1760, 1644, 1510, 1440, 1400, 1136, 758;
MS (EI) m/z 103, 115, 131, 159, 207, 237, 292; HRMS(ESI) m/z calcd
for C16H18ClO3 [M + H]+ 293.0939, found 293.0936.
4-((2-Isobutylbenzofuran-3-yl)methyl)oxetan-2-one (3au): yield
75% (48.4 mg) as a yellow oil; Rf 0.48 (petroleum ether/EtOAc 5/1);
1H NMR (400 MHz, CDCl3) δ 7.47−7.42 (m, 2H), 7.24−7.17 (m, 2H),
5.65 (t, J = 8.0 Hz, 1H), 2.80−2.76 (m, 2H), 2.73−2.63 (m, 2H), 2.62−
2.53 (m, 2H), 2.12 (dt, J = 13.6, 6.4 Hz, 2H), 0.98 (dd, J = 11.2, 6.8 Hz,
6H); 13C NMR (100 MHz, CDCl3) δ 176.7, 155.9, 154.3, 126.2, 123.9,
122.8, 119.6, 113.3, 111.2, 75.7, 35.8, 29.5, 28.8, 28.2, 22.5, 22.4 ppm;
νmax(KBr)/cm−1 3056, 2934, 1766, 1645, 1506, 1454, 1406, 1138, 749;
MS (EI) m/z 103, 115, 131, 145, 171, 215, 258; HRMS(ESI) m/z calcd
for C16H19O3 [M + H]+ 259.1329, found 259.1328.
4-((2-Isopentylbenzofuran-3-yl)methyl)oxetan-2-one (3av): yield
76% (51.7 mg) as a yellow oil; Rf 0.48 (petroleum ether/EtOAc 5/1);
1H NMR (400 MHz, CDCl3) δ 7.44 (t, J = 8.0 Hz, 2H), 7.25−7.17
(m, 2H), 5.68 (t, J = 8.0 Hz, 1H), 2.84−2.73 (m, 4H), 2.56 (dd, J = 15.6,
7.6 Hz, 2H), 1.66−1.59 (m, 3H), 0.95 (d, J = 4.0 Hz, 6H); 13C NMR
(100 MHz, CDCl3) δ 176.7, 156.8, 154.2, 126.3, 123.9, 122.8, 119.5,
112.2, 111.2, 75.7, 37.5, 29.4, 28.9, 27.7, 24.8, 22.4, 22.3 ppm;
νmax(KBr)/cm−1 3055, 2936, 1760, 1648, 1514, 1452, 1400, 1136, 756;
MS (EI) m/z 77, 85, 115, 131, 157, 185, 199, 229, 272; HRMS(ESI) m/z
calcd for C17H21O3 [M + H]+ 273.1485, found 273.1481.
4-((2-Benzylbenzofuran-3-yl)methyl)oxetan-2-one (3aw): yield
81% (51.7 mg) as a yellow oil; Rf 0.46 (petroleum ether/EtOAc 5/1);
1H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 7.6 Hz, 1H), 7.43 (d, J =
8.0 Hz, 1H), 7.30 (dd, J = 14.8, 7.6 Hz, 4H), 7.24−7.19 (m, 3H), 5.70
(t, J = 8.0 Hz, 1H), 4.17 (q, J = 16.0 Hz, 2H), 2.74−2.69 (m, 2H), 2.51−
2.44 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 176.6, 154.4, 154.1,
137.0, 128.8, 128.5, 126.9, 126.3, 124.3, 122.9, 119.7, 113.6, 111.4, 75.5,
33.2, 29.3, 28.9 ppm; νmax(KBr)/cm−1 3061, 2922, 1774, 1645, 1515,
1454, 1140, 750; MS (EI) m/z 115, 159, 178, 191, 207, 233, 292;
HRMS(ESI) m/z calcd for C19H17O3 [M + H]+ 293.1172, found
293.1170.
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 176.7, 159.2, 154.1, 126.5,
123.8, 122.7, 119.5, 111.5, 111.2, 75.7, 37.2, 32.5, 31.9, 29.5, 29.1, 26.0,
26.0 ppm; νmax(KBr)/cm−1 3060, 2928, 1776, 1648, 1506, 1450, 1144,
756; MS (EI) m/z 91, 115, 141, 169, 197, 215, 241, 270; HRMS(ESI)
m/z calcd for C17H19O3 [M + H]+ 271.1329, found 271.1325.
4-((2-Cyclohexylbenzofuran-3-yl)methyl)oxetan-2-one (3ba):
yield 85% (60.4 mg) as a yellow oil; Rf 0.33 (petroleum ether/EtOAc
1
5/1); H NMR (400 MHz, CDCl3) δ 7.48−7.42 (m, 2H), 7.25−7.17
(m, 2H), 5.73 (t, J = 8.0 Hz, 1H), 2.89−2.83 (m, 1H), 2.80−2.71 (m,
2H), 2.60−2.52 (m, 2H), 1.94−1.82 (m, 3H), 1.80−1.72 (m, 4H),
1.41−1.33 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 176.7, 160.5, 154.1,
126.3, 123.8, 122.7, 119.6, 111.2, 110.7, 75.6, 36.7, 31.9, 31.3, 29.5, 28.9,
26.3, 26.2, 25.7 ppm; νmax(KBr)/cm−1 3063, 2929, 1777, 1649, 1500,
1453, 1141, 752; MS (EI) m/z 91, 115, 145, 183, 211, 241, 256, 284;
HRMS(ESI) m/z calcd for C18H21O3 [M + H]+ 285.1485, found
285.1483.
4-((2-(Cyclopentylmethyl)benzofuran-3-yl)methyl)oxetan-2-one
(3bb): yield 73% (51.8 mg) as a yellow oil; Rf 0.44 (petroleum ether/
EtOAc 5/1); 1H NMR (400 MHz, CDCl3) δ 7.46−7.42 (m, 2H), 7.25−
7.18 (m, 2H), 5.67 (t, J = 8.0 Hz, 1H), 2.84−2.71 (m, 4H), 2.56 (dd, J =
18.0, 9.2 Hz, 2H), 2.28 (dt, J = 15.2, 7.8 Hz, 1H), 1.82−1.73 (m, 2H),
1.67−1.54 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 176.7, 156.5, 154.2,
126.2, 123.9, 122.7, 119.5, 112.6, 111.2, 75.7, 39.5, 32.5, 32.4, 29.7, 29.5,
28.8, 24.9, 24.8 ppm; νmax(KBr)/cm−1 3062, 2928, 1776, 1642, 1454,
1141, 747; MS (EI) m/z 115, 128, 131, 157, 171, 207, 216, 253, 284;
HRMS(ESI) m/z calcd for C18H21O3 [M + H]+ 285.1485, found
285.1481.
4-((2-(Cyclohexylmethyl)benzofuran-3-yl)methyl)oxetan-2-one
(3bc): yield 78% (58.1 mg) as a yellow oil; Rf 0.51 (petroleum ether/
EtOAc 5/1); 1H NMR (400 MHz, CDCl3) δ 7.44 (t, J = 8.4 Hz, 2H),
7.25−7.18 (m, 2H), 5.64 (t, J = 8.0 Hz, 1H), 2.82−2.74 (m, 2H), 2.73−
2.61 (m, 2H), 2.56 (dd, J = 20.0, 10.6 Hz, 2H), 1.81−1.64 (m, 5H), 1.18
(dd, J = 24.2, 12.8 Hz, 4H), 1.07−0.94 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 176.7, 155.6, 154.3, 126.2, 123.9, 122.7, 119.5, 113.3,
111.2, 75.8, 37.4, 34.5, 33.2, 33.1, 29.7, 29.5, 28.8, 26.2, 26.1 ppm;
νmax(KBr)/cm−1 3048, 2926, 1777, 1640, 1454, 1145, 748; MS (EI) m/z
115, 128, 131, 157, 171, 216, 254, 298; HRMS(ESI) m/z calcd for
C19H23O3 [M + H]+ 299.1642, found 299.1640.
4-((2-(Cyclohex-1-en-1-yl)benzofuran-3-yl)methyl)oxetan-2-one
(3bd): yield 78% (55.0 mg) as a yellow oil; Rf 0.42 (petroleum ether/
EtOAc 5/1); 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 7.6 Hz, 1H),
7.43 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 7.6 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H),
6.12 (s, 1H), 5.83 (t, J = 8.0 Hz, 1H), 2.81−2.77 (m, 2H), 2.64−2.59
(m, 1H), 2.56−2.52 (m, 2H), 2.45−2.34 (m, 1H), 2.32−2.23 (m, 2H),
1.83−1.76 (m, 2H), 1.75−1.68 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 176.8, 156.1, 153.8, 131.9, 128.4, 126.6, 124.4, 122.8, 120.2, 112.2,
111.3, 76.0, 29.6, 28.8, 26.7, 25.7, 22.3, 21.8 ppm; νmax(KBr)/cm−1 3040,
2931, 1735, 1542, 1452, 1102, 749; MS (EI) m/z 115, 131, 169, 181,
195, 209, 237, 282; HRMS(ESI) m/z calcd for C18H19O3 [M + H]+
283.1329, found 283.1325.
4-((2-Phenethylbenzofuran-3-yl)methyl)oxetan-2-one (3ax): yield
69% (52.8 mg) as a yellow oil; Rf 0.46 (petroleum ether/EtOAc 5/1);
1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 8.4 Hz, 1H), 7.39 (d, J =
7.6 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H), 7.24−7.16 (m, 4H), 7.08 (d, J =
7.2 Hz, 2H), 5.36 (t, J = 8.0 Hz, 1H), 3.23−3.07 (m, 2H), 3.04−3.00
(m, 2H), 2.61−2.56 (m, 2H), 2.12 (td, J = 20.0, 10.2 Hz, 1H), 1.96 (dt,
J = 12.8, 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 176.7, 154.8,
154.3, 140.5, 128.6, 128.5, 126.4, 126.2, 124.1, 122.8, 119.6, 113.6, 111.2,
75.5, 34.5, 29.3, 29.2, 28.5 ppm; νmax(KBr)/cm−1 3029, 2922, 1775,
1650, 1455, 1140, 748; MS (EI) m/z 103, 128, 145, 187, 215, 246, 281,
306; HRMS(ESI) m/z calcd for C20H19O3 [M + H]+ 307.1329, found
307.1335.
4-((2-(3-Phenylpropyl)benzofuran-3-yl)methyl)oxetan-2-one
(3ay): yield 71% (56.8 mg) as a yellow oil; Rf 0.48 (petroleum ether/
EtOAc 5/1); 1H NMR (400 MHz, CDCl3) δ 7.45 (t, J = 7.6 Hz, 2H),
7.32−7.27 (m, 3H), 7.20 (t, J = 9.0 Hz, 4H), 5.58 (t, J = 8.0 Hz, 1H), 2.81
(t, J = 7.4 Hz, 2H), 2.77−2.65 (m, 4H), 2.51 (dd, J = 16.0, 7.6 Hz, 2H),
2.10 (qd, J = 11.6, 4.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 176.6,
156.0, 154.3, 141.3, 128.5, 126.3, 126.1, 124.0, 122.8, 119.5, 112.7, 111.2,
75.5, 35.1, 29.7, 29.4, 28.8, 26.1 ppm; νmax(KBr)/cm−1 3028, 2920,
1776, 1655, 1456, 1146, 756; MS (EI) m/z 91, 119, 131, 146, 193, 207,
253, 281, 320; HRMS(ESI) m/z calcd for C21H21O3 [M + H]+
321.1485, found 321.1483.
4-((2-(Thiophen-3-yl)benzofuran-3-yl)methyl)oxetan-2-one
(3be): yield 56% (39.8 mg) as a yellow solid; mp = 114.4−115.9 °C; Rf
1
0.28 (petroleum ether/EtOAc 10/1); H NMR (400 MHz, CDCl3) δ
7.66 (s, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.46 (d,
J = 7.2 Hz, 2H), 7.33 (t, J = 7.6 Hz, 1H), 7.27 (d, J = 7.6 Hz, 1H), 5.97 (t,
J = 8.0 Hz, 1H), 2.87−2.74 (m, 2H), 2.69−2.61 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 176.6, 154.2, 149.6, 130.7, 126.9, 126.6, 126.5,
124.9, 124.8, 123.3, 120.4, 112.9, 111.5, 75.8, 29.4, 28.6 ppm;
νmax(KBr)/cm−1 3063, 2922, 1774, 1646, 1515, 1454, 1136, 750; MS
(EI) m/z 127, 152, 207, 239, 284; HRMS(ESI) m/z calcd for
C16H13O3S [M + H]+ 285.0580, found 285.0576.
3,3-Dimethyl-4-((2-phenylbenzofuran-3-yl)methyl)oxetan-2-one
(3bg): yield 87% (66.6 mg) as a yellow solid; mp = 162.6−163.8 °C; Rf
1
0.43 (petroleum ether/EtOAc 5/1); H NMR (400 MHz, CDCl3) δ
7.66 (d, J = 7.2 Hz, 2H), 7.58−7.47 (m, 5H), 7.34 (t, J = 7.6 Hz, 1H),
7.27 (d, J = 8.4 Hz, 1H), 5.86 (t, J = 8.0 Hz, 1H), 2.66−2.56 (m, 1H),
2.45−2.40 (m, 1H), 1.44 (s, 3H), 1.41 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 181.6, 154.5, 153.6, 129.9, 129.4, 128.9, 128.1, 126.9,
124.9, 123.2, 120.6, 113.3, 111.6, 72.1, 43.5, 40.8, 24.9, 24.4 ppm;
νmax(KBr)/cm−1 3060, 2930, 1771, 1646, 1516, 1498, 1119, 748; MS
4-((2-Cyclopentylbenzofuran-3-yl)methyl)oxetan-2-one (3az):
yield 79% (53.3 mg) as a yellow oil; Rf 0.37 (petroleum ether/EtOAc
5/1); 1H NMR (400 MHz, CDCl3) δ 7.44 (t, J = 8.8 Hz, 2H), 7.25−7.17
(m, 2H), 5.73 (t, J = 8.0 Hz, 1H), 3.33−3.23 (m, 1H), 2.82−2.70
(m, 2H), 2.55 (q, J = 8.0 Hz, 2H), 2.04−1.86 (m, 6H), 1.77−1.69
G
DOI: 10.1021/acs.joc.5b00154
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(EI) m/z 105, 116, 165, 194, 221, 247, 262, 306; HRMS(ESI) m/z calcd
for C20H18NaO3 [M + Na]+ 329.1148, found 329.1147.
4-((2-(4-Methoxyphenyl)benzofuran-3-yl)methyl)oxetan-2-one
(4g): yield 78% (60.1 mg) as a yellow solid; mp = 118.8−120.1 °C; Rf
1
0.43 (petroleum ether/EtOAc 2/1); H NMR (400 MHz, CDCl3) δ
4-((2-(p-Tolyl)benzofuran-3-yl)methyl)oxetan-2-one (4a): yield
89% (64.9 mg) as a yellow solid; mp = 140.5−141.3 °C; Rf 0.53
(petroleum ether/EtOAc 4/1); 1H NMR (400 MHz, CDCl3) δ 7.56 (dt,
J = 17.2, 8.4 Hz, 4H), 7.33 (t, J = 8.0 Hz, 3H), 7.27 (d, J = 8.0 Hz, 1H),
5.90 (t, J = 8.0 Hz, 1H), 2.87−2.74 (m, 2H), 2.69−2.61 (m, 2H), 2.44 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 176.7, 154.4, 154.0, 139.8, 129.6,
128.0, 126.9, 126.8, 124.8, 123.1, 120.4, 112.9, 111.6, 76.0, 29.6, 28.6,
21.4 ppm; νmax(KBr)/cm−1 3060, 2921, 1777, 1627, 1567, 1515, 1453,
1138, 749; MS (EI) m/z 109, 115, 133, 165, 178, 207, 233, 247, 292;
HRMS(ESI) m/z calcd for C19H17O3 [M + H]+ 293.1172, found
293.1170.
4-((2-(m-Tolyl)benzofuran-3-yl)methyl)oxetan-2-one (4b): yield
81% (59.1 mg) as a yellow solid; mp = 128.5−129.8 °C; Rf 0.55
(petroleum ether/EtOAc 4/1); 1H NMR (400 MHz, CDCl3) δ 7.59 (d,
J = 8.0 Hz, 1H), 7.56−7.49 (m, 2H), 7.43 (t, J = 6.4 Hz, 1H), 7.40−7.32
(m, 2H), 7.28 (d, J = 8.0 Hz, 2H), 5.92 (t, J = 8.0 Hz, 1H), 2.88−2.78 (m,
2H), 2.75−2.61 (m, 2H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
176.7, 154.4, 153.9, 138.8, 130.4, 129.7, 128.8, 128.7, 126.8, 125.3, 124.9,
123.2, 120.5, 113.3, 111.6, 75.9, 29.5, 28.6, 21.5 ppm; νmax(KBr)/cm−1
3097, 2924, 1741, 1629, 1516, 1454, 1414, 1137, 747; MS (EI) m/z 115,
137, 178, 207, 233, 267, 292; HRMS(ESI) m/z calcd for C19H17O3 [M +
H]+ 293.1172, found 293.1172.
4-((7-Methyl-2-phenylbenzofuran-3-yl)methyl)oxetan-2-one (4c):
yield 85% (62.1 mg) as a yellow solid; mp = 116.7−119.2 °C; Rf 0.56
(petroleum ether/EtOAc 4/1); 1H NMR (400 MHz, CDCl3) δ 7.61 (d,
J = 7.6 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.40 (dd, J = 15.0, 7.6 Hz, 2H),
7.35 (d, J = 7.2 Hz, 2H), 7.29 (t, J = 7.6 Hz, 2H), 5.55 (t, J = 8.0 Hz, 1H),
2.74 (dt, J = 18.9, 13.6 Hz, 2H), 2.67−2.56 (m, 1H), 2.49 (td, J = 12.0,
6.8 Hz, 1H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 176.6, 154.7,
154.6, 138.6, 130.8, 130.7, 130.1, 128.9, 126.1, 125.8, 124.8, 123.1, 120.3,
114.7, 111.7, 75.8, 29.4, 28.4, 20.1 ppm; νmax(KBr)/cm−1 3038, 2926,
1744, 1628, 1515, 1451, 1410, 1136, 749; MS (EI) m/z 115, 152, 178,
207, 219, 233, 247, 292; HRMS(ESI) m/z calcd for C19H17O3 [M + H]+
293.1172, found 293.1168.
7.61−7.56 (m, 3H), 7.52 (d, J = 8.0 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H),
7.27 (d, J = 6.4 Hz, 1H), 7.03 (d, J = 8.0 Hz, 2H), 5.88 (t, J = 8.0 Hz, 1H),
3.88 (s, 3H), 2.89−2.75 (m, 2H), 2.73−2.56 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 176.7, 160.6, 154.3, 154.0, 129.6, 126.9, 124.6,
123.1, 122.2, 120.3, 114.4, 112.2, 111.5, 76.1, 55.4, 29.6, 28.5 ppm;
νmax(KBr)/cm−1 3066, 2921, 1774, 1645, 1511, 1454, 1137, 753; MS
(EI) m/z 115, 135, 147, 177, 191, 207, 249, 281, 308; HRMS(ESI) m/z
calcd for C19H17O4 [M + H]+ 309.1121, found 309.1120.
4-((6-Methoxy-2-phenylbenzofuran-3-yl)methyl)oxetan-2-one
(4h): yield 76% (58.5 mg) as a yellow solid; mp = 115.3−116.8 °C; Rf
1
0.45 (petroleum ether/EtOAc 2/1); H NMR (400 MHz, CDCl3) δ
7.60 (d, J = 7.6 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.42 (t, J = 8.0 Hz, 1H),
7.35 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 7.6 Hz, 1H), 7.21 (d, J = 6.4 Hz, 2H),
7.01 (d, J = 8.0 Hz, 1H), 5.93 (t, J = 8.0 Hz, 1H), 3.89 (s, 3H), 2.87−2.76
(m, 2H), 2.74−2.59 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 176.6,
160.0, 154.4, 153.5, 130.9, 130.0, 126.7, 125.0, 123.2, 120.6, 120.5, 115.2,
113.7, 113.6, 111.7, 75.8, 55.5, 29.5, 28.6 ppm; νmax(KBr)/cm−1 3060,
2926, 1776, 1642, 1510, 1453, 1138, 758; MS (EI) m/z 126, 145, 165,
181, 207, 249, 279, 308; HRMS(ESI) m/z calcd for C19H17O4 [M + H]+
309.1121, found 309.1118.
4-((5-Fluoro-2-phenylbenzofuran-3-yl)methyl)oxetan-2-one (4i):
yield 80% (59.2 mg) as a yellow solid; mp = 194.4−195.7 °C; Rf 0.50
1
(petroleum ether/EtOAc 4/1); H NMR (400 MHz, CDCl3) δ 7.65
(d, J = 7.2 Hz, 1H), 7.54−7.41 (m, 4H), 7.24−7.19 (m, 1H), 7.06 (t, J =
8.8 Hz, 1H), 5.87 (t, J = 8.0 Hz, 1H), 2.88−2.72 (m, 2H), 2.68−2.60 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 176.3, 159.2 (d, J = 238.1 Hz),
155.5, 150.7, 129.6 (d, J = 35.5 Hz), 129.0, 128.1, 127.4, 126.4, 113.7 (d,
J = 16.8 Hz), 112.7 (d, J = 26.2 Hz), 112.4 (d, J = 9.6 Hz), 106.3 (d, J =
25.5 Hz), 75.5, 29.4, 28.6 ppm; νmax(KBr)/cm−1 3058, 2926, 1768, 1642,
1508, 1450, 1135, 756; MS (EI) m/z 105, 118, 139, 165, 183, 207, 237,
251, 296; HRMS(ESI) m/z calcd for C18H14FO3 [M + H]+ 297.0921,
found 297.0918.
4-((5-Chloro-2-phenylbenzofuran-3-yl)methyl)oxetan-2-one (4j):
yield 68% (53.0 mg) as a yellow solid; mp = 198.7−199.8 °C; Rf 0.56
(petroleum ether/EtOAc 4/1); 1H NMR (400 MHz, CDCl3) δ 7.65 (d,
J = 7.2 Hz, 2H), 7.56−7.45 (m, 5H), 7.30 (d, J = 8.0 Hz, 1H), 5.86 (t, J =
8.0 Hz, 1H), 2.84−2.73 (m, 2H), 2.67−2.58 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 176.3, 155.2, 152.9, 129.9, 129.3, 129.0, 128.9,
128.2, 128.1, 125.2, 120.2, 113.1, 112.6, 75.4, 29.4, 28.7 ppm;
νmax(KBr)/cm−1 3066, 2924, 1777, 1646, 1516, 1448, 1136, 755; MS
(EI) m/z 105, 147, 201, 218, 255, 267, 312; HRMS(ESI) m/z calcd for
C18H13ClNaO3 [M + Na]+ 335.0445, found 335.0442.
4-((2-(4-Ethylphenyl)benzofuran-3-yl)methyl)oxetan-2-one (4d):
yield 85% (65.0 mg) as a yellow solid; mp = 138.8−140.3 °C; Rf 0.59
(petroleum ether/EtOAc 4/1); 1H NMR (400 MHz, CDCl3) δ 7.58 (d,
J = 8.0 Hz, 3H), 7.53 (d, J = 8.0 Hz, 1H), 7.33 (t, J = 8.2 Hz, 3H), 7.27 (d,
J = 8.0 Hz, 1H), 5.91 (t, J = 8.0 Hz, 1H), 2.88−2.78 (m, 2H), 2.73 (q, J =
7.6 Hz, 2H), 2.69−2.57 (m, 2H), 1.29 (t, J = 7.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 176.7, 154.4, 154.1, 146.0, 128.5, 128.1, 127.1,
126.8, 124.8, 123.1, 120.4, 112.9, 111.6, 76.0, 29.6, 28.8, 28.6, 15.4 ppm;
νmax(KBr)/cm−1 3032, 2924, 1776, 1628, 1515, 1454, 1416, 1138, 752;
MS (EI) m/z 115, 133, 178, 207, 233, 251, 281, 297, 306; HRMS(ESI)
m/z calcd for C20H18NaO3 [M + Na]+ 329.1148, found 329.1146.
4-((2-(4-(tert-Butyl)phenyl)benzofuran-3-yl)methyl)oxetan-2-one
(4e): yield 81% (67.6 mg) as a yellow solid; mp = 137.9−139.5 °C; Rf
4-((6-Chloro-2-phenylbenzofuran-3-yl)methyl)oxetan-2-one (4k):
yield 79% (61.6 mg) as a yellow solid; mp = 173.3−175.0 °C; Rf 0.54
1
(petroleum ether/EtOAc 4/1); H NMR (400 MHz, CDCl3) δ 7.64
(d, J = 7.6 Hz, 2H), 7.55−7.46 (m, 5H), 7.25 (d, J = 6.8 Hz, 1H), 5.89
(t, J = 8.0 Hz, 1H), 2.88−2.77 (m, 2H), 2.69−2.57 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 176.4, 154.5, 154.3, 130.9, 129.8, 129.3, 129.0,
128.0, 125.5, 123.9, 121.2, 113.4, 112.2, 75.6, 29.4, 28.8 ppm;
νmax(KBr)/cm−1 3035, 2921, 1741, 1646, 1515, 1464, 1138, 754; MS
(EI) m/z 77, 128, 165, 207, 218, 255, 267, 283, 312; HRMS(ESI) m/z
calcd for C18H14ClO3 [M + H]+ 313.0626, found 313.0623.
1
0.62 (petroleum ether/EtOAc 4/1); H NMR (400 MHz, CDCl3) δ
7.59 (t, J = 6.4 Hz, 3H), 7.53 (d, J = 8.4 Hz, 3H), 7.33 (d, J = 7.6 Hz, 1H),
7.27 (d, J = 8.4 Hz, 1H), 5.92 (t, J = 8.0 Hz, 1H), 2.86−2.73 (m, 2H),
2.72−2.57 (m, 2H), 1.37 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 176.7,
154.4, 154.0, 152.9, 127.9, 126.9, 126.8, 125.9, 124.8, 123.1, 120.5, 112.9,
111.6, 76.0, 34.9, 31.2, 29.6, 28.6 ppm; νmax(KBr)/cm−1 3057, 2959,
1778, 1619, 1509, 1455, 1400, 1135, 747; MS (EI) m/z 105, 119, 133,
154, 193, 207, 249, 281, 334; HRMS(ESI) m/z calcd for C22H22NaO3
[M + Na]+ 357.1461, found 357.1458.
4-((5-Bromo-2-phenylbenzofuran-3-yl)methyl)oxetan-2-one (4l):
yield 87% (77.4 mg) as a yellow solid; mp = 207.5−208.6 °C; Rf 0.55
1
(petroleum ether/EtOAc 4/1); H NMR (400 MHz, CDCl3) δ 7.71
(s, 1H), 7.63 (t, J = 7.6 Hz, 2H), 7.57−7.47 (m, 3H), 7.30 (d, J = 8.0 Hz,
2H), 5.85 (t, J = 8.0 Hz, 1H), 2.87−2.78 (m, 2H), 2.65−2.59 (m, 2H);
13C NMR (100 MHz, CDCl3) δ 176.3, 155.0, 153.2, 133.7, 129.9, 129.2,
129.0, 128.2, 128.1, 127.9, 123.2, 116.4, 113.1, 75.4, 29.5, 28.7 ppm;
νmax(KBr)/cm−1 3056, 2928, 1756, 1648, 1510, 1442, 1138, 758; MS
(EI) m/z 115, 147, 207, 267, 305, 356; HRMS(ESI) m/z calcd for
C18H14BrO3 [M + H]+ 357.0121, found 357.0117.
4-((2-(2,4-Dimethylphenyl)benzofuran-3-yl)methyl)oxetan-2-one
(4f): yield 76% (58.1 mg) as a yellow solid; mp = 99.3−100.7 °C; Rf 0.61
(petroleum ether/EtOAc 4/1); 1H NMR (400 MHz, CDCl3) δ 7.60 (d,
J = 7.6 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.34 (t, J = 7.2 Hz, 1H), 7.29 (d,
J = 7.6 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.16 (s, 1H), 7.10 (d, J = 7.6 Hz,
1H), 5.54 (t, J = 8.0 Hz, 1H), 2.79−2.67 (m, 2H), 2.64−2.45 (m, 2H),
2.40 (s, 3H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 176.7, 154.9,
154.7, 140.2, 138.4, 131.6, 130.7, 126.5, 126.2, 126.0, 124.7, 123.1, 120.2,
114.4, 111.6, 75.9, 29.5, 28.4, 21.3, 20.1 ppm; νmax(KBr)/cm−1 3061,
2924, 1776, 1646, 1516, 1453, 1138, 752; MS (EI) m/z 117, 152, 165,
178, 205, 232, 247, 306; HRMS(ESI) m/z calcd for C20H18NaO3
[M + Na]+ 329.1148, found 329.1145.
4-((6-Bromo-2-phenylbenzofuran-3-yl)methyl)oxetan-2-one
(4m): yield 81% (72.1 mg) as a yellow solid; mp = 188.9−189.8 °C; Rf
1
0.50 (petroleum ether/EtOAc 4/1); H NMR (400 MHz, CDCl3) δ
7.72 (s, 1H), 7.64 (d, J = 7.2 Hz, 2H), 7.59−7.45 (m, 4H), 7.37
(dd, J = 16.0, 8.0 Hz, 1H), 5.89 (t, J = 8.0 Hz, 1H), 2.80 (dd, J = 10.8,
H
DOI: 10.1021/acs.joc.5b00154
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
7.6 Hz, 2H), 2.61 (dd, J = 17.6, 8.0 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 176.4, 154.7, 154.2, 129.8, 129.0, 128.1, 126.6, 125.9, 121.5,
120.9, 118.3, 115.1, 113.5, 75.5, 29.4, 28.8 ppm; νmax(KBr)/cm−1 3038,
2926, 1740, 1648, 1516, 1468, 1133, 756; MS (EI) m/z 115, 133, 176,
233, 327, 356; HRMS(ESI) m/z calcd for C18H14BrO3 [M + H]+
357.0121, found 357.0119.
0.01 mmol), 4l (35.6 mg, 0.1 mmol), CH3ONa (7.6 mg, 0.3 mmol),
sodium p-toluenesulfinic acid (18.0 mg, 0.1 mmol), and cyclohexane
(0.3 mL). The reaction vessel was closed under air, and the result-
ing solution was stirred at 160 °C for 4 h. After cooling to room
temperature, the volatiles were removed under vacuum and the residue
was purified by column chromatography (silica gel, petroleum ether/
ethyl acetate = 5/1) to give the corresponding product 11b (24.1 mg) as
a yellow solid in 68% yield.
4-((5,6-Dichloro-2-phenylbenzofuran-3-yl)methyl)oxetan-2-one
(4n): yield 74% (64.0 mg) as a yellow solid; mp = 233.8−234.9 °C; Rf
1
0.36 (petroleum ether/EtOAc 2/1); H NMR (400 MHz, CDCl3) δ
4-((2,5-Diphenylbenzofuran-3-yl)methyl)oxetan-2-one (11b):
7.78 (s, 1H), 7.62−7.49 (m, 4H), 7.38 (t, J = 7.6 Hz, 1H), 7.30 (d, J =
7.6 Hz, 1H), 5.86 (t, J = 8.0 Hz, 1H), 2.90−2.76 (m, 2H), 2.73−2.63 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 176.3, 154.5, 150.9, 133.8, 133.4,
130.9, 129.7, 127.0, 126.4, 125.6, 123.5, 120.8, 111.8, 75.3, 29.3, 28.6
ppm; νmax(KBr)/cm−1 3036, 2928, 1748, 1642, 1519, 1464, 1138, 758;
MS (EI) m/z 77, 103, 131, 171, 191, 207, 281, 314, 346; HRMS(ESI)
m/z calcd for C18H13Cl2O3 [M + H]+ 347.0236, found 347.0233.
3-Chloro-2-phenylbenzofuran (6a):19 yield 84% (47.9 mg) as a
white solid; mp = 68.4−69.8 °C; Rf 0.67 (petroleum ether/EtOAc
100/1); 1H NMR (400 MHz, CDCl3) δ 7.66 (t, J = 8.8 Hz, 2H), 7.53
(d, J = 8.0 Hz, 1H), 7.23−7.11 (m, 4H), 7.03 (dt, J = 14.4, 7.6 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ 154.4, 152.0, 130.5, 129.5, 128.6, 128.5,
126.3, 124.9, 123.1, 120.7, 111.3, 107.7 ppm; HRMS(ESI) m/z calcd for
C14H9ClNaO [M + Na]+ 251.0234, found 251.0232.
yield 68% (24.1 mg) as a yellow solid; mp = 195.3−196.8 °C; Rf 0.41
1
(petroleum ether/EtOAc 4/1); H NMR (400 MHz, CDCl3) δ 7.74
(s, 1H), 7.69 (d, J = 7.2 Hz, 2H), 7.61 (d, J = 8.4 Hz, 3H), 7.58−7.50
(m, 4H), 7.49−7.44 (m, 2H), 7.37 (t, J = 7.2 Hz, 1H), 5.93 (t, J = 8.0 Hz,
1H), 2.88−2.79 (m, 2H), 2.77−2.61 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 176.5, 154.5, 154.1, 141.4, 137.1, 129.7, 129.6, 128.9, 128.8,
128.2, 127.6, 127.3, 127.1, 124.8, 119.0, 113.5, 111.8, 75.8, 29.6,
28.6 ppm; νmax(KBr)/cm−1 3048, 2926, 1769, 1646, 1515, 1508, 1500,
1456, 1411, 1400, 1136, 758; MS (EI) m/z 133, 163, 191, 207, 281, 354;
HRMS(EI) m/z calcd for C24H19O3 [M +H]+ 355.1329, found 355.1326.
General Procedure for the Synthesis of 11c. Following a
reported procedure,16 under nitrogen, ZnCl2 (0.5 M solution in THF;
0.35 mL, 0.16 mmol) was added by syringe to a Schlenk tube.
o-Tolylmagnesium chloride (1.0 M solution in THF; 0.4 mL,
0.40 mmol) was then added dropwise, and the resulting mixture was
stirred at room temperature for 20 min. Next, NMP (0.5 mL) was added
by syringe, followed after 5 min by Pd(P(t-Bu)3)2 (1.5 mg, 0.003 mmol)
and 4l (35.6 mg, 0.1 mmol). The Schlenk tube was closed at the Teflon
stopcock, and the reaction mixture was stirred in a 100 °C oil bath for
2 h. It was then allowed to cool to room temperature, and aqueous HCl
was added (1.0 M; 3 mL). The resulting mixture was extracted with Et2O
(2 × 10 mL), and the organic extracts were combined, washed with
water (2 × 10 mL), dried (MgSO4), and concentrated, affording a
yellow solid. Column chromatography on silica (petroleum ether/ethyl
acetate = 5/1) furnished 24.9 mg (63%) of the title compound 11c as a
yellow solid.
3-Chloro-2-propylbenzofuran (6b): yield 66% (32.0 mg) as a yellow
1
oil; Rf 0.71 (petroleum ether/EtOAc 100/1); H NMR (400 MHz,
CDCl3) δ 7.31 (d, J = 8.4 Hz, 1H), 7.27−7.25 (m, 1H), 7.21 (d, J =
7.6 Hz, 2H), 2.77 (t, J = 7.2 Hz, 2H), 1.72 (dd, J = 14.8, 7.2 Hz, 2H), 0.93
(t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 158.9, 154.3, 131.1,
125.1, 124.5, 123.1, 120.8, 110.9, 29.7, 21.3, 13.7 ppm; νmax(KBr)/cm−1
3026, 2926, 1648, 1510, 1463, 1136; MS (EI) m/z 63, 77, 102, 115, 131,
160, 194; HRMS(ESI) m/z calcd for C11H11ClNaO [M + Na]+
217.0391, found 217.0388.
2-Phenylbenzofuran (7a):18c yield 11% (5.5 mg) as a white solid;
1
mp = 108.5−109.8 °C; Rf 0.61 (petroleum ether/EtOAc 100/1); H
NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 7.2 Hz,
1H), 7.51 (d, J = 8.0 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), 7.35 (d, J = 6.8 Hz,
1H), 7.26 (d, J = 8.0 Hz, 1H), 7.22 (t, J = 7.2 Hz, 1H), 7.01 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 156.0, 154.9, 130.5, 129.3, 128.8, 128.6,
125.0, 124.3, 123.0, 120.9, 111.2, 101.3 ppm.
4-((2-(4′-Propyl-[1,1′-biphenyl]-4-yl)benzofuran-3-yl)methyl)-
oxetan-2-one (11c): yield 63% (24.9 mg) as a yellow solid; mp =
1
203.5−204.7 °C; Rf 0.51 (petroleum ether/EtOAc 4/1); H NMR
(400 MHz, CDCl3) δ 7.73 (s, 4H), 7.61 (d, J = 7.6 Hz, 2H), 7.56 (t, J =
6.8 Hz, 2H), 7.35 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 7.6 Hz, 3H), 5.97 (t, J =
7.6 Hz, 1H), 2.89−2.80 (m, 2H), 2.77−2.69 (m, 2H), 2.67−2.63 (m,
2H), 1.70 (dd, J = 14.8, 7.6 Hz, 2H), 0.99 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 176.7, 154.5, 153.6, 142.7, 142.3, 137.4, 129.1,
128.4, 128.3, 127.4, 126.9, 126.8, 124.9, 123.2, 120.5, 113.4, 111.7, 75.9,
37.7, 29.5, 28.6, 24.5, 13.9 ppm; νmax(KBr)/cm−1 3058, 2923, 1775,
1648, 1517, 1456, 1428, 1137, 751; MS (EI) m/z 135, 177, 191, 207,
249, 281, 313, 355, 396; HRMS(EI) m/z calcd for C27H25O3 [M +H]+
397.1798, found 397.1797.
2-Propylbenzofuran (7b):20 yield 19% (7.6 mg) as a yellow oil; Rf
0.64 (petroleum ether/EtOAc 100/1); 1H NMR (400 MHz, CDCl3) δ
7.47 (d, J = 7.2 Hz, 1H), 7.40 (d, J = 7.6 Hz, 1H), 7.17 (dt, J = 13.2,
6.8 Hz, 2H), 6.36 (s, 1H), 2.73 (t, J = 7.6 Hz, 2H), 1.82−1.71 (m, 2H),
1.00 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.6, 154.7,
129.1, 123.0, 122.4, 120.2, 110.7, 101.9, 30.5, 21.1, 13.8 ppm.
General Procedure for the Synthesis of 11a. Following a
reported procedure,16 to a mixture of (4-ethylphenyl)boronic acid (45.0
mg, 0.30 mmol), Pd(OAc)2 (5 mol %), K3PO4 (63.5 mg, 0.30 mmol),
and Xphos (4.8 mg, 0.01 mmol) in 1 mL of toluene was added a solution
of 4l (35.6 mg, 0.10 mmol) in 1.0 mL of toluene under nitrogen.
After stirring at 110 °C for 10 h, the reaction mixture was quenched
with water, extracted with ethyl acetate, washed with brine, dried
over MgSO4, and concentrated. Column chromatography on silica
(petroleum ether/ethyl acetate = 5/1) gave 28.7 mg (yield: 75%) of 11a
as a yellow solid.
ASSOCIATED CONTENT
* Supporting Information
Spectral data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Authors
*Fax: (+86) 20-8711-2906. E-mail: lisryang@scut.edu.cn.
*Fax: (+86) 20-8711-2906. E-mail: jianghf@scut.edu.cn.
4-((5-(4-Ethylphenyl)-2-phenylbenzofuran-3-yl)methyl)oxetan-2-
one (11a): yield 75% (28.7 mg) as a yellow solid; mp = 197.6−198.8 °C;
Rf 0.44 (petroleum ether/EtOAc 4/1); 1H NMR (400 MHz, CDCl3) δ
7.75 (s, 1H), 7.68 (d, J = 7.6 Hz, 2H), 7.64 (d, J = 8.0 Hz, 1H), 7.58 (d,
J = 8.0 Hz, 2H), 7.55−7.47 (m, 4H), 7.31 (d, J = 8.0 Hz, 2H), 5.93 (t, J =
8.0 Hz, 1H), 2.89−2.79 (m, 2H), 2.77−2.63 (m, 4H), 1.30 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 176.6, 155.2, 154.0, 143.6, 138.7,
138.3, 129.8, 129.5, 128.9, 128.4, 128.1, 127.3, 125.7, 122.7, 120.6, 113.5,
109.8, 75.9, 29.7, 28.7, 28.5, 15.6 ppm; νmax(KBr)/cm−1 3050, 2928,
1776, 1648, 1516, 1500, 1456, 1418, 1400, 1135, 757; MS (EI) m/z 126,
207, 281, 335, 382; HRMS(EI) m/z calcd for C26H22NaO3 [M + Na]+
405.1461, found 405.1455.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful to the National Natural Science
Foundation of China (21490572 and 21420102003), National
Basic Research Program of China (973 Program) (2011CB808600),
and the Fundamental Research Funds for the Central Universities
(2014ZP0004) for financial support.
General Procedure for the Synthesis of 11b. Following a
reported procedure,17 an oven-dried pressure tube (10 mL) was charged
with Pd(OAc)2 (1.5 mg, 0.005 mmol), tri-p-tolylphosphine (3.0 mg,
I
DOI: 10.1021/acs.joc.5b00154
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
X. Chem. Commun. 2013, 49, 6611−6613. (d) Zhu, R.; Wei, J.; Shi, Z.
Chem. Sci. 2013, 4, 3706−3711. (e) Liu, G.; Shen, Y.; Zhou, Z.; Lu, X.
Angew. Chem., Int. Ed. 2013, 52, 6033−6037. (f) Rao, V. K.; Shelke, G.
M.; Tiwari, R.; Parang, K.; Kumar, A. Org. Lett. 2013, 15, 2190−2193.
(g) Yuan, F.-Q.; Han, F.-S. Adv. Synth. Catal. 2013, 355, 537−547.
(h) Okitsu, T.; Nakata, K.; Nishigaki, K.; Michioka, N.; Karatani, M.;
Wada, A. J. Org. Chem. 2014, 79, 5914−5920. (i) Murakami, K.;
Yorimitsu, H.; Osuka, A. Angew. Chem., Int. Ed. 2014, 53, 7510−7513.
(j) Yuan, W.; Ma, S. Org. Lett. 2014, 16, 193−195.
REFERENCES
■
(1) For selected reviews, see: (a) Horvat
́
h, I. T.; Anastas, P. T. Chem.
Rev. 2007, 107, 2169−2173. (b) Gunanathan, C.; Milstein, D. Acc.
Chem. Res. 2011, 44, 588−602. (c) Sundararaju, B.; Achard, M.;
Bruneau, C. Chem. Soc. Rev. 2012, 41, 4467−4483. (d) Sheldon, R. A.
Chem. Soc. Rev. 2012, 41, 1437−1451.
(2) For selected reviews, see: (a) Zeni, G.; Larock, R. C. Chem. Rev.
2006, 106, 4644−4680. (b) Patil, N. P.; Yamamoto, Y. Chem. Rev. 2008,
108, 3395−3442. (c) Li, B.-J.; Shi, Z.-J. Chem. Soc. Rev. 2012, 41, 5588−
5598. (d) Wu, W.; Jiang, H. Acc. Chem. Res. 2012, 45, 1736−1748.
(e) Chow, W. K.; Yuen, O. Y.; Choy, P. Y.; So, C. M.; Lau, C. P.; Wong,
W. T.; Kwong, F. Y. RSC Adv. 2013, 3, 12518−12539. (f) Gulevich, A.
V.; Dudnik, A. S.; Chernyak, N.; Gevorgyan, V. Chem. Rev. 2013, 113,
3084−3213.
(12) Li, J.; Yang, W.; Yang, S.; Huang, L.; Wu, W.; Sun, Y.; Jiang, H.
Angew. Chem., Int. Ed. 2014, 53, 7219−7222.
(13) (a) Huang, J.; Zhou, L.; Jiang, H. Angew. Chem., Int. Ed. 2006, 45,
1945−1949. (b) Huang, L.; Wang, Q.; Liu, X.; Jiang, H. Angew. Chem.,
Int. Ed. 2012, 51, 5696−5700. (c) Wu, W.; Gao, Y.; Jiang, H.; Huang, Y.
J. Org. Chem. 2013, 78, 4580−4586. (d) Huang, L.; Wang, Q.; Wu, W.;
Jiang, H. J. Org. Chem. 2014, 79, 7734−7739. (e) Wu, W.; Jiang, H. Acc.
Chem. Res. 2014, 47, 2483−2504. (f) Zhang, Z.; Ouyang, L.; Wu, W.; Li,
J.; Zhang, Z.; Jiang, H. J. Org. Chem. 2014, 79, 10734−10742.
(14) (a) Yang, S.-R.; Jiang, H.-F.; Li, Y.-Q.; Chen, H.-J.; Luo, W.; Xu,
Y.-B. Tetrahedron 2008, 64, 2930−2937. (b) Li, J.; Yang, S.; Huang, L.;
Chen, H.; Jiang, H. RSC Adv. 2013, 3, 11529−11532. (c) Li, J.; Yang, S.;
Jiang, H.; Wu, W.; Zhao, J. J. Org. Chem. 2013, 78, 12477−12486. (d) Li,
J.; Yang, S.; Wu, W.; Qi, C.; Deng, Z.; Jiang, H. Tetrahedron 2014, 70,
1516−1523. (e) Li, J.; Yang, S.; Wu, W.; Jiang, H. Chem. Commun. 2014,
50, 1381−1383.
(3) For selected reviews: (a) Nicolaou, K. C.; Edmonds, D. J.; Bulger,
P. G. Angew. Chem., Int. Ed. 2006, 45, 7134−7186. (b) Tietze, L. F.;
Brasche, G.; Gericke, K. Domino Reactions in Organic Synthesis; Wiley-
VCH, Weinheim, 2006; p 672. (c) Pellissier, H. Tetrahedron 2006, 62,
2143−2173.
(4) For selected reviews: (a) Skoda-Fcļ des, R. Chem. Rev. 2003, 103,
4095−4130. (b) Cacchi, S.; Fabrizi, G. Chem. Rev. 2011, 111, PR215−
PR283. (c) Magano, J.; Dunetz, J. R. Chem. Rev. 2011, 111, 2177−2250.
(5) For selected examples: (a) Durani, N.; Jain, R.; Saeed, A.; Dikshit,
D. K.; Durani, S.; Kapil, R. S. J. Med. Chem. 1989, 32, 1700−1707.
(b) Wallez, V.; Durieux-Poissonnier, S.; Chavatte, P.; Boutin, J. A.;
Audinot, V.; Nicolas, J.-P.; Bennejean, C.; Delagrange, P.; Renard, P.;
Lesieur, D. J. Med. Chem. 2002, 45, 2788−2800. (c) Ohno, M.;
Miyamoto, M.; Hoshi, K.; Takeda, T.; Yamada, N.; Ohtake, A. J. Med.
Chem. 2005, 48, 5279−5294. (d) He, Y.; Xu, J.; Yu, Z.-H.; Gunawan, A.
M.; Wu, L.; Wang, L.; Zhang, Z.-Y. J. Med. Chem. 2013, 56, 832−842.
(6) (a) Gilman, H.; Melstrom, D. S. J. Am. Chem. Soc. 1948, 70, 1655−
1657. (b) Larock, R. C.; Harrison, L. W. J. Am. Chem. Soc. 1984, 106,
4218−4227. (c) Kondo, Y.; Shiga, F.; Murata, N.; Sakamoto, T.;
Yamanaka, H. Tetrahedron 1994, 50, 11803−11812. (d) Arcadi, A.;
Cacchi, S.; Rosario, M. D.; Fabrizi, G.; Marinelli, F. J. Org. Chem. 1996,
61, 9280−9288. (e) Inoue, M.; Carson, M. W.; Frontier, A. J.;
Danishefsky, S. J. J. Am. Chem. Soc. 2001, 123, 1878−1889. (f) Han, Z.;
Zhang, L.; Li, Z.; Fan, R. Angew. Chem., Int. Ed. 2014, 53, 6805−6809.
(15) See the Supporting Information for details.
(16) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176−
4211.
(17) Zhao, F.; Tan, Q.; Xiao, F.; Zhang, S.; Deng, G. J. Org. Lett. 2013,
15, 1520−1523.
(18) (a) Chaplin, J. H.; Flynn, B. L. Chem. Commun. 2001, 1594−1595.
(b) Nakamura, M.; Ilies, L.; Otsubo, S.; Nakamura, E. Angew. Chem., Int.
Ed. 2006, 45, 944−947. (c) Zhou, R.; Wang, W.; Jiang, Z.; Wang, K.;
Zheng, X.; Fu, H.; Chen, H.; Li, R. Chem. Commun. 2014, 50, 6023−
6026.
(19) Liang, Y.; Tang, S.; Zhang, X.-D.; Mao, L.-Q.; Xie, Y.-X.; Li, J.-H.
Org. Lett. 2006, 8, 3017−3020.
(20) Li, X.; Chianese, A. R.; Vogel, T.; Crabtree, R. H. Org. Lett. 2005,
7, 5437−5440.
́
(7) Martínez, C.; Alvarez, R.; Aurrecoechea, J. M. Org. Lett. 2009, 11,
1083−1086.
(8) (a) Clough, J. M.; Mann, I. S.; Widdowson, D. A. Tetrahedron Lett.
1987, 28, 2645−2648. (b) Trejo, A.; Arzeno, H.; Browner, M.; Chanda,
S.; Cheng, S.; Comer, D. D.; Dalrymple, S. A.; Dunten, P.; Lafargue, J.;
Lovejoy, B.; Lim, J.; McIntosh, J.; Miller, J.; Papp, E.; Reuter, D.;
Roberts, R.; Sanpablo, F.; Saunders, J.; Song, K.; Villasenor, A.; Warren,
S. D.; Welch, M.; Weller, P.; Whiteley, P. E.; Zeng, L.; Goldstein, D. M. J.
Med. Chem. 2003, 46, 4702−4713.
(9) For direct C2-arylation of benzofurans: (a) Hughes, C. C.;
Trauner, D. Angew. Chem., Int. Ed. 2002, 41, 1569−1572. (b) Do, H.-Q.;
Khan, R. M. K.; Daugulis, O. J. Am. Chem. Soc. 2008, 130, 15185−15192.
́
(c) Liegault, B.; Lapointe, D.; Caron, L.; Vlassova, A.; Fagnou, K. J. Org.
Chem. 2009, 74, 1826−1834. (d) Matsuda, S.; Takahashi, M.;
Monguchi, D.; Mori, A. Synlett 2009, 1941−1944. (e) Tamba, S.;
Okubo, Y.; Tanaka, S.; Monguchi, D.; Mori, A. J. Org. Chem. 2010, 75,
6998−7001. For direct C3-arylation of benzofurans: (f) Ionita, M.;
Roger, J.; Doucet, H. ChemSusChem 2010, 3, 367−376. (g) Roy, D.;
Mom, S.; Royer, S.; Lucas, D.; Hierso, J.-C.; Doucet, H. ACS Catal.
2012, 2, 1033−1041. (h) Carrer, A.; Brinet, D.; Florent, J.-C.; Rousselle,
̈
P.; Bertounesque, E. J. Org. Chem. 2012, 77, 1316−1327.
(10) (a) Dwight, T. A.; Rue, N. R.; Charyk, D.; Josselyn, R.; DeBoef, B.
Org. Lett. 2007, 9, 3137−3139. (b) Kuhl, N.; Hopkinson, M. N.; Glorius,
F. Angew. Chem., Int. Ed. 2012, 51, 8230−8234. (c) Dong, J.; Long, Z.;
Song, F.; Wu, N.; Guo, Q.; Lan, J.; You, J. Angew. Chem., Int. Ed. 2013,
52, 580−584. (d) Lee, J. H.; Kim, M.; Kim, I. J. Org. Chem. 2014, 79,
6153−6163.
(11) For recent representative examples: (a) Markina, N. A.; Chen, Y.;
Larock, R. C. Tetrahedron 2013, 69, 2701−2713. (b) Kuram, M. R.;
Bhanuchandra, M.; Sahoo, A. K. Angew. Chem., Int. Ed. 2013, 52, 4607−
4612. (c) Zeng, W.; Wu, W.; Jiang, H.; Huang, L.; Sun, Y.; Chen, Z.; Li,
J
DOI: 10.1021/acs.joc.5b00154
J. Org. Chem. XXXX, XXX, XXX−XXX